1. Field of the Invention
The invention generally relates to newly identified isolates of canine distemper virus (CDV). In particular, the invention provides improved CDV immunogenic compositions, vaccines and diagnostics that contain or take into account these newly discovered isolates, and describes a systematic protocol for selecting, based on genetic makeup, broad spectrum isolates for use in immunogenic compositions, vaccines and diagnostics.
2. Background of the Invention
Canine distemper virus (CDV) is a single-stranded RNA Morbillivirus that affects dogs of all ages. CDV causes a multi-systemic infection that may involve the ocular, respiratory, gastrointestinal, integument and nervous systems, and is usually rapidly fatal. While the disease is a devastating problem for dogs, other species are also susceptible to the virus, for example, raccoons, foxes, coyotes, wolves, various fur-producing animals, and large non-domestic cats such as lions, leopards, cheetahs, and tigers. In the past, vaccines have proven to be effective in reducing the incidence of CDV infection. However, there appears to be a resurgence of the incidence of CDV, even in fully vaccinated animals.
The hemagglutinin (H) protein of CDV is a viral surface protein that is involved in host cell-virus binding, and mutations in the protein affect host cell-virus interactions. H protein is considered to be a virulence factor for CDV. The H protein displays significant (e.g. about 10%) variation in amino acid sequence among CDV isolates, and phylogenetic analysis of this variation serves as the basis for the division of viral isolates into seven lineages: American-1, American-2, Arctic-like, Asia-1, Asia-2, Europe, and European wildlife (McCarthy, A. J., M. A. Shaw, and S. J. Goodman. 2007. Proc. Biol. Sci. 274:3165-3174). Antibodies to H protein provide protection against infection, and are thus the likely basis for vaccine efficacy. However, antibodies do not necessarily cross-react between lineages. Hence, vaccines based on a particular isolate may or may not provide the vaccine recipient with protection against infection with other isolates. This is particularly problematic given 1) the high rate of mutation exhibited by RNA viruses such as CDV and 2) the increase in the global transport of dogs from one country to another, which fosters the introduction of new lineages into territories where they were previously unknown. Further, for dogs vaccinated with a particular CDV isolate, exposure to a genetically distant CDV may lead to sequestration of the incoming CDV virus in immunologically privileged sites (e.g. brain, ganglion, spinal cord, central, autonomic nervous systems, nasal plenum and bladder epithelium), allowing the propagation and spread of the genetically distant CDV without detection, since neurological symptoms may be overlooked by veterinary practitioners due to lack of sensitivity of the diagnostic tests and expense of long term treatment of a neurological patient.
Unfortunately, CDV vaccines currently in use have not been updated for about 60 years (Woma et al., 2010. Phylogenetic analysis of the hemagglutinin gene of the current wild-type canine distemper viruses from South Africa:Lineage Africa.Vet. Microbiol. doi:10.1016/jvet-mic.2009.11.013) and have not kept pace with these changes. The use of these outdated vaccines is the likely cause of recent outbreaks of CDV infection, since these vaccines may not provide protection against infection with newly emerging lineages of CDV. Moreover, PCR sequencing has revealed that the vaccine isolate used in one commercial vaccine was misidentified (Demeter et al., 2009: Controversial results of the genetic analysis of a canine distemper vaccine strain. Vet. Microbiol. Published Online), further complicating the problem of determining how to best detect, monitor, and prevent CDV infection and transmission.
Clearly, epidemiological studies to investigate the rise in CDV clinical cases are warranted, as is the development of new immunological and vaccine compositions and diagnostic methods that take into account emerging isolates of CDV.